It was found that immunization of mice with small amounts of inactivated Moloney leukemia virus (MoLV) increases tumorigenesis by Moloney sarcoma virus (MS-M). During the past year it was observed that similar increases in tumorigenesis can be obtained in the simian adenovirus 7 (SA7) system. When hamsters were immunized with 10 to the 6th power particles of SA7, they showed a significantly increased tumor incidence relative to non-immunized controls. Immunization with 10 to the 4th power or 10 to the 10th power particles of SA7 resulted in tumor incidences that were comparable to controls. Similar results were obtained in the Friend virus (FV) system with one exception: the strain of mice used was a critical factor. BALB/cJ mice demonstrated a significantly increased incidence of FV-induced mortality compared to controls, after they had been immunized with 10 to the 6th power particles of inactivated FV. However, no significant difference in FV-induced tumor incidence was observed after BALB/cByJ mice were immunized with any amount of inactivated FV (10 to the 2nd power to 10 to the 10th power particles have been evaluated). This difference is not associated with the major histocompatibility complex, since both BALB/cJ and BALB/cByJ mice are genotypically H-2d/H2-d. In vitro assays have been performed in an effort to correlate the incidence of tumorigenesis with the immune reactivity of lymphocytes derived from mice immunized with varying amounts of inactivated MoLV. It was previously observed that differential reactivities were observed when spleen cells from mice immunized with varying amounts of MoLV were evaluated in the 3H-thymidine post-label assay. In these studies the mice were sacrificed to obtain the spleen cells. When hemisplenectomies were performed in order to both obtain spleen cells and to keep the mice alive, no correlation was observed between tumor development and spleen cell reactivity of individual mice. Future studies will attempt to utilize systems that may demonstrate more pronounced in vitro reactivity in order to define the mechanism of the stimulatory effect of low dose immunization.